The primary objective of the work planned is to develop a specific therapy, not now existent, for sickle cell disease. Pathogenic events in this disease depend on the formation of a relatively rigid intraerythrocytic gel consisting of polymeric fibers of deoxyhemoglobin S. Accordingly, the physical chemistry and rheology of the gel and the gelation process will be studied. Rheological studies will be directed toward viscous and plastic properties of the gel and its thixotropy. Cone-plate viscometers and related instrumentation for measurements of stress and strain will be used. Physical chemical studies will be directed toward elucidation of the two equilibria contributing to gelation, polymerization and separation into conjugate isotropic and anistropic phases, and toward the existence and properties of metastable and polymorphic states. Correlations between gel phase structure and other aspects of physical chemistry will be made with rheological properties. Finally, theoretical studies on the nature of phase chnges in systems of reversibly polymerizing theoretical studies on the nature of phase changes in systems of reversibly polymerizing fibers are planned, hemoglobin S gelation being an example of such a system.